Wang Ping, Song Yeunjoo E, Lynn Audrey, Miskimen Kristy, Gulyayev Alex, Prough Michael B, Dorfsman Daniel A, Laux Renee A, Fuzzell Sarada L, Hochstetler Sherri D, Zaman Andrew F, Adams Larry D, Caywood Laura J, Clouse Jason E, Herington Sharlene D, Whitehead Patrice, Liu Yining, Moore Noel, Ogrocki Paula, Lerner Alan J, Griswold Anthony J, Vance Jeffery M, Cuccaro Michael L, Scott William K, Pericak-Vance Margaret A, Haines Jonathan L
Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA.
Cleveland Institute for Computational Biology, 2103 Cornell Road, Cleveland, OH 44106, USA.
medRxiv. 2025 May 21:2025.05.13.25327557. doi: 10.1101/2025.05.13.25327557.
Plasma biomarkers for Alzheimer disease (AD) hold promise for disease diagnosis and prediction, yet their genetic underpinnings remain underexplored.
We measured plasma amyloid beta 40 (Aβ40), Aβ42, Aβ42/Aβ40, total tau (t-tau), phosphorylated tau 181 (p-tau181), Aβ42/t-tau, Aβ42/p-tau181, neurofilament light chain, and glial fibrillary acidic protein in the Midwestern Amish. Pedigree-based heritability was estimated from multigenerational pedigrees, and SNP-based heritability was derived from single nucleotide polymorphisms (SNPs).
Among all Amish individuals, additive genetic effects explained 11.1% to 36.6% of biomarker variances. estimates were consistently lower, ranging from 6.7% to 28.7%. The heritability of these biomarkers in subgroups of cognitively normal individuals and ε4 non-carriers yielded similar results.
Plasma biomarkers such as amyloid β, t-tau, and p-tau181 are moderately heritable in the Amish, underscoring the impact of genetic determinants of plasma biomarkers associated with AD.
阿尔茨海默病（AD）的血浆生物标志物有望用于疾病诊断和预测，但其遗传基础仍未得到充分探索。
我们测量了美国中西部阿米什人中血浆淀粉样蛋白β40（Aβ40）、Aβ42、Aβ42/Aβ40、总tau蛋白（t-tau）、磷酸化tau蛋白181（p-tau181）、Aβ42/t-tau、Aβ42/p-tau181、神经丝轻链和胶质纤维酸性蛋白。基于家系的遗传力是从多代家系中估计出来的，基于单核苷酸多态性（SNP）的遗传力是从单核苷酸多态性中推导出来的。
在所有阿米什个体中，加性遗传效应解释了生物标志物变异的11.1%至36.6%。估计值一直较低，范围为6.7%至28.7%。这些生物标志物在认知正常个体和ε4非携带者亚组中的遗传力产生了相似的结果。
淀粉样β蛋白、t-tau和p-tau181等血浆生物标志物在阿米什人中具有中等遗传性，这突出了与AD相关的血浆生物标志物遗传决定因素的影响。
